Breast cancer is the second leading cause of death due to cancer among women in the United States. In 2007, approximately 213,000 women will be diagnosed with breast cancer, and about 41,000 of those will die from the disease this year. Obesity increases the risk of getting breast cancer (and dying from breast cancer) in post-menopausal women. The population of obese adult women has increased dramatically in the United States -- from approximately 16% in 1962 to more than 34% today. The dramatic increase in obesity, combined with the fact that over 75% of new cases of breast cancer occur in postmenopausal women, increases the likelihood that the harmful impact of obesity on breast cancer will continue to rise. The mechanism(s) by which obesity increases breast cancer risk is not known. We do know, however, that obesity can cause a condition called "insulin resistance," in which the body does not respond properly to insulin. Post-menopausal women are at increased risk for this condition. Both obesity and insulin-resistance increase the risk for breast cancer. Our animal studies will fill important gaps in our knowledge of the obesity-to-breast cancer relationship, since they will determine how adipose tissue and insulin resistance affect breast cancer development (pre- vs. post menopause). Our studies are unique in this respect, since nearly all published animal studies examining the obesity-to-breast cancer relationship have failed to take ovarian hormones and menopause into consideration. By examining the roles adipose tissue and high insulin levels play in the development of breast cancer in the context of ovarian function (pre- vs. post- menopause), we will be able to use breast cancer animal models more effectively, and what we learn from these models will be relevant to humans. Results from our studies, especially those involving estrogen (to examine pre- vs. post-menopause) and IGF 1 (to examine insulin resistance), could serve as the basis for the development of more specific targets to prevent and treat breast cancer in both pre- and post-menopausal women. Dr. Nunez received post-doctoral training at the National Institute of Diabetes and Kidney Diseases and subsequently at the National Cancer Institute, in the prestigious Cancer Prevention Fellowship Program. He received extensive training in the field of cancer prevention, energy balance, and their relationships to cancer risk. Dr. Nunez accepted a position as an Assistant Professor at the University of Texas at Austin in the fall of 2005. The K-22 career development award will enable the candidate to establish an academic laboratory that will focus on elucidating the roles of adipose tissue and insulin resistance in breast cancer development.